Note: Descriptions are shown in the official language in which they were submitted.
~247;~7
X-4939 -1-
PROCESS FOR PREPARING N-CHLOROIMIDES
This invention relates to a process for the
manufacture of N-chlorophthalimide, N-chlorosuccinimide,
or N-chloroglutarimide.
The principal prior art processes for pre-
paring N-chloroimides customarily have employed an
aqueous reaction medium. In general, such processes
can be classified as follows:
(1) Chlorination of the corresponding imide
using an inorganic hypochlorite in a mixture of acetic
acid and water;
~ 2) Chlorination by passing chlorine into an
aqueous solution comprising equivalent amounts of the
corresponding imide and a strong base, e.g., sodium
hydroxide or potassium hydroxide;
~ 3) Chlorination of the corresponding imide
using t-butyl hypochlorite in a mixture of t-butyl
alcohol and water.
Of the above general methods, only method (2)
involves the use of molecular chlorine. However,
because of the presence of the aqueous system, this
method has been found to have serious drawbacks.
First, chlorine is only very slightly soluble in water,
Secondly, and more importantly, it is known that an
imide, when present in an alkaline aqueous medium such
as would re~ult from potassium or sodium hydroxide and
water, undergoes rapid hydrolysis. When, for example,
phthalimide is subjected to alkaline aqueous conditions,
the following decomposition sequence occurs:
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l~Z~
X-4939 -2-
~3~ a o
~ OH
Even more importantly, it has been established
[Arthur R. Hurwitz, "Degradation of N-Chlorosuccinimide
in Aqueous Solution", Diss. Abst., B, 28 (3), 971
~1967)] that an N-chloroimide product, when present in
an agueous alkaline medium, such as would be the case
under the conditions of chlorination provided by method
(2) above, degrades with possible formation of the
highly explosive and toxic gas, nitrogen trichloride.
The following sequences are postulated for the decom-
position of N-chlorosuccinimide:
,
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X-4 93 9 -3-
Z Z
+ /~\
+ ' I
O O C~
+-~I`o~ .
/ j\ I
~¦ + +
+ I /~\
C~
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X-4~39 -4-
Non-aqueous processes for preparing N-chloro
compounds have been few. U.S. Patent No. 2,686,203
describes a process for preparing N-halo-t-alkyl
cyanamides by treating a t-alkyl cyanamide with molecular
chlorine in an inert solvent in the presence of a molar
equivalent of a halogen acid acceptor, typically
pyridine. U.S. Patent No. 4,082,766 discloses a method
for preparing N-chlorophthalimide under substantially
non-aqueous reaction conditions by contacting an alkali
metal salt of phthalimide with chlorine in the presence
of a halogenated aliphatic hydrocarbon at a temperature
of from about -10C. to about +40C. This prior art
process does not employ an HCl acceptor.
An even more advantageous method employs a
substantially non-aqueous medium and permits use of the
imide itself as starting material instead of the
previously required alkali metal salt. The N-chloro-
imide is prepared by contacting the corresponding imide
with molecular chlorine at a temperature of from
about -10C. to about +50C. under substantially
non-aqueous conditions in the presence of (l) an epoxy
compound in an amount representing at least about one
epoxy moiety per each imide moiety and (2) at least a
catalytic amount of a tertiary amine. (This method is
the subject of Belgian Patent 872,584 issued ~une 7,
1979).
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~247;î~7
X-4939 -5-
The preparation of N-chlorophthalimide (NCP)
by the reaction of chlorine with phthalimide (Y=H) or
an alkali metal salt of phthalimide (Y=alkali metal) is
depicted below:
~Y + Cl~ -Cl ~ YCI
(NCP)
The reaction is an equilibrium, and, in order to obtain
NCP in satisfactory yield, reaction conditions must be
found that will favor NCP production. In the processes
of the prior art where the chlorination reaction is
performed in an aqueous medium, the production of NCP
is favored since NC~ is removed (precipitates) because
of its relative insolubility in water. In the processes
of the prior art where the chlorination reaction is
performed employing an alkali metal salt of phthalimide
in a non-aqueous medium (a chlorinated hydrocarbon),
the production of NCP is favored since the alkali metal
chloride salt (YCl) is removed (precipitates) because
of its relative insolubility in the non-aqueous solvent.
2~ The present invention provides a process for
preparing N-chlorophthalimide, N-chlorosuccinimide or
N-chloroglutarimide which comprises contactlng
phthalimide, succinimide or ~lutarimide with molecular
chlorine under substantially non-aqueous cor.ditions,
utilizing an inert organic solvent, in the presence of
a cross-linked polyvinylpyridine copolymer, said copolymer
containing between about 1% and about 10% cross linking.
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X-d939 -6-
The polyvinylpyridine copolymer is weakly
basic and is insoluble in organic solvents. The
copolymer effects the rapid removal of hydrogen chloride
from the reaction medium and shifts the reaction
equilibrium to favor N-chloroimide formation. Further,
the vinylpyridine copolymer can be readily removed from
the reaction medium by filtration or other suitable
means.
Whereas the use of an epoxy compound for
removing hydrogen chloride during the reaction of an
imide with chlorine require the presence of a tertiary
amine catalyst (e.g. quinoline), as described in the
aforesaid Belgian Patent 872,584, the use of the
vinylpyridine copolymer does not require the use of a
lS tertiary amine catalyst. Comparable yields are obtained
in the process with or without a tertiary amine catalyst.
In practicing the process of the invention,
the chlorine can be introduced into the reaction medium
containing the desired imide either by passing the gas
directly into the reaction medium or by first absorbing
chlorine onto the polymer and then adding the polymer-
chlorine complex to the reaction medium. It will be
understood that both techniques are within the scope of
; the invention.
In the reaction of chlorine with the imide
moiety one mole of chlorine is consumed for each mole
of available imide moiety. Therefore, it is highly
preferred that at least one mole of chlorine is present
per each mole of imide moiety. Even more preferably,
about a 10% molar excess of chlorine is ~rousht into
contact with the imide. The temperature at which the
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27
X-4939 -7-
reaction is carried out generally ranges from about
-10C. to about ~50C. and, preferably, from about
-5C. to about +25C. The reaction generally is
completed after a period of from about 1 hour to about
24 hours, and, preferably, is carried out over a period
of from about 3 to 15 hours.
The reaction between the imide and chlorine
is carried out in an inert organic solvent under sub-
stantially non-aqueous conditions. The term "sub-
stantially non-aqueous conditions" does not mean the
total absence of water fxom the reaction system;
instead, this term prescribes the exercise of reason-
able precautions to ensure its preclusion, including
the avoidance of any deliberate addition of water to
the reaction medium prior to or during the time in
which the reaction is being effected. Amounts of water
which are customarily present in such commercial
solvents and reactants as may be employed in the
process of this invention need not first be removed in
order to comply with the "substantially non-aqueous"
re~uirement. By the term "solvent" is meant a medium
which partially or completely solubilizes the imide
starting material. The term "inert" defines a solvent
which generally does not react with the reactants,
principally, with the chlorine, under the conditionq of
the proces~. Typical such solvents are halogenated
aromatic and aliphatic hydrocarbons. Examples of
halogenated aromatic hydrocarbons are chlorobenzene,
1,2-dichlorobenzene, 1,4-dichlorobenzene, bromobenzene,
and the like~ Examples of halogenated aliphatic
hydrocarbons are methylene chloride, chloroform,
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X-4939 -8-
1,1,2-trichloroethane, 1,2-dichloroethane, 1,1-
dichloroethane, l,l,l-trichloroethane, and the like.
of the above, the halogenated aliphatic hydrocarbons
are preferred, and, of these, the preferred solvent is
S methylene chloride.
The cross-linked polyvinylpyridine polymers
employed in the process of this invention are weakly
basic resins which are insoluble in the inert organic
solvents and, in particular! the reaction medium
employed in the present process. The polymers contain
cross-linking of from about 1~ to about 10%.
The cross-linked polyvinylpyridine polymer is
prepared by polymerizing vinylpyridine monomer in the
presence of the cross-linking agent. The term "vinyl-
pyridine" is used herein to mean 4-vinylpyridine, 3-
vinylpyridine, 2-vinylpyridine and the methylated
vinylpyridines such as 2-methyl-4-vinylpyridine and
3-methyl-4-vinylpyridine. 4-Vinylpyridine is the
preferred monomer. The polyvinylpyridines can be
cross-linked with a wide variety of known cross-
linking agents. Examples of cross-linking agents are
the difunctional agents such as vinyl aromatics, for
example, divinylbenzene, the acrylamides such as
O
N,N'-methylenebisaCrylamide [CH2~NH-C-CH-CH2)2], and
N,N'~decamethylenebisacrylamide, and N,N-diallyl-
acrylamide; the acrylate and methylacrylate esters
such as ethylene diacrylate, ethylene dimethylacrylate,
and triethyleneglycol dimethacrylate; the allyl
esters of aromatic and aliphatic dicarboxylic acids
such as diallyl phthalate, diallyl malonate, and
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X-4939 _9_
diallyl succinate; and other difunctional vinyl and
allyl agents such as divinylsulfone and N,N'-
diallylpiperazine; the trifunctional cross-linking
agents for example, l,l,l-trimethylolpropane tri-
O
methacrylate [CH3CH2-C(O-C-C(CH3)=CH2)3], 1,1,1-
trimethylolpropane triacrylate, l,l,l-trimethylol-
ethane triacrylate, l,l,l-irimethylolethane tri-
methacrylate, 1,3,5-triacryloylhexahydro-s-triazine,
1,3,5-trimethacryloylhexahydro-s-triazine, trivinyl-
cyclohexane, and triallyl isocyanurate; and tetra-
functional cross-linking agents, ~or example, penta-
erythritol tetramethacrylate, pentaerythritol tetra-
methacrylate, tetraallyloxyethane, and tetraallyl-
pyromellitate.
~ preferred cross-linking agent is divinyl-
benzene. Other preferred agents are methylenebis-
acrylamide and methylenebismethacrylamide represented
respectively by the following formulae
.. .. ..
CH2=CH-C-NH-CH2-NH-C-CH=CH2
,0, 0
CH2=C-C-NH-CH2-NH-C-C=CH2
CH3 CH3
The vinylpyridine monomer can also be
cross-linked with a divinylpyridine or a methylated
divinylpyridine e.g. 2-methyl-4,6-divinylpyridine. It
will be readily appreciated that other known or
X-4939 -10-
preparable cross-linking agents can be used to prepare
the cross-linked polyvinylpyridine polymer used in the
process of this invention.
Preferred cross-linked polymers of this
invention are poly-(4-vinylpyridine)divinylbenzene
(containing about 2 percent to about 5 percent cross-
linking), poly-(4-vinylpyridine)-N,N'-methylene-
bisacrylamide and poly-(4-vinylpyridine)-N,N'-
methylenebismethacrylamide.
The polyvinylpyridine polymers are prepared
conveniently by heating the vinylpyridine in the
presence of azobisisobutyronitrile and the cr~ss-
linking agent in aqueous solvent system. A suitable
aqueous solvent system which can be used is saline
solution and diisobutylketone. The saline solution
p~omotes polymerization in the organic phase thus
providing for a more complete polymerization.
The polymerization can also be carried out
as described by Hallensleben and Wurm, Angew. Chem.
Int. Ed. En~l. 15, 163 (1976) wherein the preparation
of poly-(4-vinylpyridine)-divinylbenzene is described.
Alternatively the cross-linked polymers can
be prepared in water via emulsion polymerization with
surfactants such as polyvinyl alcohol or polyethylene
oxide. Macroreticular beads of the cross-linked
polymers can be prepared by procedures known in the
art, for example, as described by U.S. Patent No.
3,816,355.
The cross-linking agents described herein
are commercially available compounds and can be
prepared by known methods.
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X-4939 -11-
It will be appreciated by those practicing
in the chemical arts that while the polymers formed
with the different cross-linking agents are functional
equivalents in the process, individual cross-linked
polymers may have certain advantageous properties not
shared by others. For example, certain of the polymers
can be regenerated and reused numerous times while
others withstand less regeneration and reuse.
Further, some of the cross-linked polymers
are more readily washed free of impurities than others
following their preparation. Likewise, some polymers
are more costly than others. Also, with certain
starting materials a lesser amount of one polymer may
be required than with others.
The preferred extent of cross-linking in the
polymer is between about 2% and about 5~. The desired
range of cross-linking is obtained by using the appro-
priate amount of the cross-linking agent in the poly-
merization of the vinylpyridine. The polyvinylpyridine
having the desired cross-linking rapidly absorbs the
hydrogen chloride formed during the reaction of the
phthalimide, succinimide or glutarimide with chlorine.
Further, since the polymer is insoluble in the reaction
medium, the acid is rapidly and completely removed from
the reaction system. This rapid removal of the acid
side product shifts the equilibrium of the reaction to
favor chlorination.
The cross-linked polyvinylpyridine can be
used in a variety of forms. For example, it can be in
the form of a fine po~der or in the form of small
beads, or in the form of macroporous beads. Preferably
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~24~27
X-~939 -12-
the form of the copolymer has a high surface area which
is a measure of the availability of the basic sites of
the polymer to the acid. Accordingly, the lower the
average particle size of the polymer the higher will be
the surface area and the greater availability of basic
groups. Likewise, the copolymer in the form of macro-
porous beads has a high surface area including internal
surface area with concomitant high exposure of the
basic group~ in the o~lymer. Fbr a ~ olymer which is in the form
of relatively unif~0~y sh~ particles such as h~a~q, for example
o~lymers in the form of macroreticular beads, the pref~n~d size is
between about 20 microns and about 120 microns in
diameter.~br a copolymer of irregular particle shape,
such as may be obtained by crushing the copolymer resin
in a hammer mill, the preferred particle size is
obtained by collecting the particles passing through a
sieve of about 120 mesh.
Copolymers having a cross-linking content of
between about 1% and about 10% display characteristic
swelling in the organic solvents employed in the
process. ~opolymers having a higher cross-linking
content swell to a lesser degree and, the extent of
swelling decreases as the extent of cross-linking
increases. The increased volume of the copolymer due
to swelling allows for greatly enhanced access to the
basic sites in the polymer by hydrogen chloride.
Copolymers which are cross-linked to greater than 10%
swell much less than those which are cross-linked to
less than 10%, or within the preferred range, and
although insoluble in the organic solvents are not
efficient HCl binders.
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X-4939 -13-
The ratio of the amount of polymer employed
per amount of imide starting material is preferably
between about 1:1 and about 1:5 by weight, most
preferably, the ratio is about 1:2 to about 1:3.
N-Chlorophthalimide, N-chlorosuccinimide and
N-chloroglutarimide produced by the process of this
invention are highly useful reagents for carrying out
chlorination reactions which require a source of
positive chlorine. Examples of such reactions are, for
example, oxidation of sulfides, alcohols, amines, and
imines; chlorination of amines, reactive aromatic
systems, carbonyl compounds having ~-hydrogens, and the
like.
The following Examples further illustrate the
process of this invention.
Example 1
Preparation of poly~4-vinylpyridine)-divinylbenzene
copolymer.
To a 2-liter, 3-necked round bottom flask
were added 1100 ml. of water and 4.8 g. of poly(vinyl
alcohol) and the solution was heated under nitrogen to
80C. A solution of 50 g. of 4-vinylpyridine and
3.0 g. of divinylbenzene in 100 ml. of toluene was
rapidly added with stirring to the hot solution,
followed by the addition of 2 g. of azobisisobutyrani-
trile. The copolymer began to form at once and the
suspension was stirred vigorously at 80C. for about 16
hours.
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X-4939 -14-
The copolymer was collected by filtering the
reaction mixture through cloth and was washed extensively
with water, acetone, diethyl ether, methylene chloride
and lastly with methyl alcohol. Swelling was encountered
during the diethyl ether washing and with the methylene
chloride and methyl alcohol washings. The copolymeric
resin was then dried ln vacuo to yield 45.05 g. of the
dried resin.
The resin was finished by grinding and col-
lecting the material which passed through 60 meshsieve.
The nitrogen content of the resin was 12.35%
as determined by combustion.
Example 2
N-Chlorophthalimide (Method A).
To 2.45 g. of 4-vinylpyridine-divinylbenzene
copolymer (7.38 mcg./g., 10% excess) in 200 ml. of
methylene chloride was introduced chlorine until the
solvent turned slightly greenish yellow. Phthalimide
(7.35 g, 50 ~M) was added in one portion. Quinoline
(three drops) was added, and the reaction mixture was
stirred at room temperature for five hours.
The reaction mixture was filtered to remove
reacted and unreacted polymer. The polymer was washed
twice with methylene chloride tl5 ml.). The original
filtrate and the washing were combined and evaporated
slowly to about one-third volume. White crystals
formed at this step, but the mixture was kept in a
refrigerator overnight to complete the crystallization.
The crystals were collected by filtration. After
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~247Z7
X-4939 -15-
drying under vacuum, there was obtained 8.70 g. (95.9%
yield) of the title product, m.p. 179.5-180C., iden-
tified by infrared spectral analysis. Percent chlorine:
Found 17.6; calculated 19.5%.
Repeating the above procedure but omitting
the quinoline catalyst there was obtained 8.05 g. of
the title product, m.p. 180-183C. (Yield 88.7~).
Percent chlorine: Found, 10.7; calculated 19.5%. The
infrared spectra of the product is identical to that
obtained above.
Example 3
N-Chlorophthalimide (Method B~.
To 7.45 g. of 4-vinylpyridine-divinylbenzene
15 copolymer (55 mM/eg), in 100 ml. of methylene chloride,
was added chlorine until there was produced a persistent
yellow color in the solvent. The polymer was collected
by filtration under slight vacuum. The wet polymer-
chlorine complex was then placed in 100 ml. of phthal-
imide (7.35 g.). The mixture was stirred at room
temperature for three hours. By thin layer chroma-
tography, it was shown that at least 50% of the phthal-
imide is converted to the N-chlorinated product.
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